The objective of this research is to define the series of distinctive cytological changes that cells in their nuclear layer of the retina undergo to become mature and functional. Differentiation of bipolar and horizontal cells and their synaptic contacts will be analyzed by the Golgi technique and conventional EM in normal mice and either genetically or light-induced photoreceptor degeneration. Two mouse mutants, pcd or rd, with different genetic lesions resulting in complete photoreceptor cell death over very different time periods, will be examined. The morphological response of cells in the inner nuclear layer, under three very different conditions of removal of primary input, will be analyzed. The inner layers of the retina will serve as a model for plasticity of neuronal elements in other areas of the CNS when the primary input is removed. In addition to differentiation, the involvement of glycoproteins and other polysaccaride-containing macromolecules in cell surface interactions during synapse formation will be studied in the retina to gain insight into the area of inter-neuronal recognition. Cell surface characteristics will be investigated by using peroxidase- or ferritin-conjugated plant lectins.